Cost-effectiveness analysis of infected necrotizing pancreatitis management in an academic setting.

BACKGROUND AND AIMS: Traditional management for infected necrotizing pancreatitis (INP) often utilizes open necrosectomy, which carries high morbidity and complication rates. Thus, minimally invasive strategies have gained favor, specifically step-up approaches utilizing endoscopic or minimally-invasive surgery (MIS); however, the ideal management modality for INP has not been identified. METHODS: A decision tree model was designed to analyze costs and survival associated with open necrosectomy, endoscopic step-up, and MIS step-up protocols for management of INP after 4 weeks of necrosis development with adequate retroperitoneal access. Costs were based on a third-party payer perspective using Medicare reimbursement rates. The model's effectiveness was represented by quality-adjusted life-years (QALYs). Sensitivity analyses were performed to validate results. RESULTS: Endoscopic step-up was the dominant economic strategy with 7.92 QALYs for $90,864.09. Surgical step-up resulted in a decrease of 0.09 QALYs and a cost increase of $10,067.89 while open necrosectomy resulted in a decrease of 0.4 QALYs and an increased cost of $18,407.52 over endoscopic step-up. In 100,000 random-sampling simulations, 65.5% of simulations favored endoscopic step-up. MIS step-up was favored when MIS acute mortality rates fell and when MIS drainage success rates rose. CONCLUSIONS: In our simulated patients with INP, the most cost-effective management strategy is endoscopic step-up. Cost-effectiveness varies with changes in acute mortality and drainage success, which will depend on local expertise.

Cost-effectiveness of palliative emergent surgery versus endoscopic stenting for acute malignant colonic obstruction.

BACKGROUND: Endoscopic stenting has demonstrated value over emergent surgery as a palliative intervention for patients with acute large bowel obstruction due to advanced colorectal cancer. However, concerns regarding high reintervention rates and the risk of perforation have brought into question its cost-effectiveness. METHODS: A decision tree analysis was performed to analyze costs and survival in patients with unresectable or metastatic colorectal cancer who present with acute large bowel obstruction. The model was designed with two treatment arms: self-expanding metallic stent (SEMS) placement and emergent surgery. Costs were derived from medicare reimbursement rates (US$), while effectiveness was represented by quality-adjusted life years (QALYs). The primary outcome measure was the incremental cost-effectiveness ratio (ICER). The model was tested for validation using one-way, two-way, and probabilistic sensitivity analyses. RESULTS: Endoscopic stenting resulted in an average cost of $43,798.06 and 0.68 QALYs. Emergent surgery cost $5865.30 more, while only yielding 0.58 QALYs. This resulted in an ICER of - $58,653.00, indicating that SEMS placement is the dominant strategy. One-way and two-way sensitivity analyses demonstrated that emergent surgery would require an improved survival rate in comparison to endoscopic stenting to become the favored treatment modality. In 100,000 probabilistic simulations, endoscopic stenting was favored 96.3% of the time. CONCLUSIONS: In patients with acute colonic obstruction in the presence of unresectable or metastatic disease, endoscopic stenting is a more cost-effective palliative intervention than emergent surgery. This recommendation would favor surgery over SEMS placement with improved surgical survival, or if the majority of patients undergoing stenting required reintervention.

Design of an immunohistochemistry biomarker panel for diagnosis of pancreatic adenocarcinoma.

BACKGROUND: Challenges still exist in differentiating pancreatic adenocarcinoma from benign disease. The use of adjuvant testing of tissue biopsies has demonstrated potential diagnostic value. We designed a proof of concept study to first validate four individual immunohistochemistry biomarkers and then combine them into a panel to boost overall diagnostic sensitivity. METHODS: Malignant and benign pancreas from 27 pancreaticoduodenectomy specimens underwent immunohistochemistry staining with VHL, IMP3, S100A4, S100P. Using ROC curve analysis, threshold criteria for number of cells staining were chosen for each biomarker. Biomarkers were then evaluated as a panel for their ability to discriminate malignant from benign specimens. RESULTS: Diagnostic sensitivity of VHL, IMP3, S100A4, and S100P were 75.0%, 79.2%, 45.8%, and 0%. When VHL, IMP3, and S100A4 were grouped into a panel, they were able to distinguish cancer from normal tissue with a sensitivity of 100% and a specificity of 96%. CONCLUSIONS: The high diagnostic value of an IHC panel consisting of VHL, IMP3, and S100A4 on surgical specimens suggests the need for future prospective studies of these biomarkers on biopsy specimens.

Time Trends and Predictors of Acute Gastroenteritis in the United States: Results From National Health and Nutrition Examination Survey 2005-2014.

GOALS: To investigate the time trends of the prevalence and predictors of acute gastroenteritis (AGE) in the United States from 2005 to 2014 using nationally representative data. BACKGROUND: AGE results in numerous visits to emergency departments and outpatient clinics annually in the United States with the estimated attributable cost to the US economy up to $145 billion dollars. However, time trends and predictors of AGE are not fully understood. METHODS: Data were obtained from the National Health and Nutrition Survey (NHANES) 2005 to 2014, a nationally representative health survey. AGE was defined by a medical question (Do you have a stomach or intestinal illness with vomiting or diarrhea that started during last 30 d?). Prevalence of AGE was estimated in the total population as well as by selected demographic variables. Predictors of AGE and time trends of prevalence over survey periods were also investigated. RESULTS: Overall monthly prevalence of AGE was 8.31% (95% confidence interval, 7.81-8.81), corresponding to 22.8 million people. AGE was associated with a younger age group, the highest in ages 0 to 9 years old, females, winter to early spring season, US born, divorced/separated/widowed individuals, current smokers, heavy alcohol users, and low household income. In the trends analyses, the prevalence of AGE significantly decreased over the study periods: 10.23% in 2005 to 2006, 9.89% in 2007 to 2008, 7.58% in 2009 to 2010, 6.44% in 2011 to 2012, and 7.47% in 2013 to 2014 (trend P<0.001). CONCLUSION: In the United States from 2005 to 2014, the monthly prevalence of AGE was 8.31% and has been significantly decreasing over time.

Obesity, Metabolic Syndrome, and Cardiovascular Risk in Gluten-Free Followers Without Celiac Disease in the United States: Results from the National Health and Nutrition Examination Survey 2009-2014.

BACKGROUND: Despite unclear benefits of gluten-free diets (GFD) in the general population, gluten-free followers without medical indications are driving the market. Few studies have investigated health benefits of GFD in the general population. AIMS: To estimate metabolic and cardiovascular disease (CVD) risk profiles among gluten-free followers without celiac disease (CD). METHODS: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2009-2014. There were 13,523 persons without CD who had GFD information. People with known CVD were excluded. We compared gluten-free followers without CD and the general population by selective metabolic and CVD risk profiles using survey-weighted generalized logistic regression. RESULTS: There were 155 gluten-free followers without CD and CVD, corresponding to a weighted prevalence of 1.3% (3.2 million Americans). Gluten-free followers tended to be women and have a smaller waist circumference and higher HDL cholesterol. They also had a lower BMI with a borderline p value (0.053) and significant self-reported weight loss (-1.33 kg) over one year. Moreover, gluten-free followers were more likely to consider their weight appropriate. There was no statistical difference by age, smoking, hypertension, total cholesterol, triglyceride cholesterol, HbA1c, or fasting glucose. Despite a lower probability of having metabolic syndrome (33.0 vs 38.5%) and lower 10-year CVD risk score (4.52 vs 5.70%) in gluten-free followers, there was no statistical difference. CONCLUSIONS: Although being on a GFD may be beneficial in weight management, there was no significant difference in terms of prevalence of metabolic syndrome and CVD risk score in gluten-free followers without CD.

Impact and outcomes of research sponsored by the American Society for Gastrointestinal Endoscopy.

BACKGROUND AND AIMS: Since 1985, the American Society for Gastrointestinal Endoscopy (ASGE) has awarded grants for endoscopic-related research. The goals of this study were to examine trends in ASGE grant funding and to assess productivity of previous recipients of the ASGE grant awards. METHODS: This was a retrospective cohort analysis of all research grants awarded by the ASGE through 2009. Measures of academic productivity and self-assessment of the ASGE awards' impact on the recipients' careers were defined by using publicly available resources (eg, National Library of Medicine-PubMed) and administration of an electronic survey to award recipients. RESULTS: The ASGE awarded 304 grants totaling $12.5 million to 214 unique awardees. Funding increased 7.5-fold between 1985 and 1989 (mean $102,000/year) and between 2005 and 2009 (mean $771,000/year). The majority of awardees were men (83%), were at or below the level of assistant professor (82%), with a median of 3 years of postfellowship experience at the time of the award, and derived from a broad spectrum of institutions as measured by National Institutes of Health funding rank (median 26, interquartile range [IQR] 12-64). Nineteen percent had a master's degree in a research-related field. Awardees' median publications per year increased from 3.5 (IQR 1.2-9.0) before funding to 5.7 (IQR 1.8-9.5) since funding; P = .04, and median h-index scores increased from 3 (IQR 1-8) to 17 (IQR 8-26); P < .001. Multivariate analysis found that the presence of a second advanced degree (eg, masters or doctorate) was independently predictive of high productivity (odds ratio [OR] 2.92; 95% confidence interval [CI], 1.09-7.81). Among 212 unique grant recipients, 82 (40%) completed the online survey. Of the respondents, median peer-reviewed publications per year increased from 3.4 (IQR 1.9-5.5) to 4.5 (IQR 2.0-9.5); P = .17. Ninety-one percent reported that the ASGE grant had a positive or very positive impact on their careers, and 85% of respondents are currently practicing in an academic environment. Most of the grants resulted in at least 1 peer-reviewed publication (67% per Internet-based search and 81% per survey). CONCLUSIONS: The ASGE research program has grown considerably since 1985, with the majority of grants resulting in at least 1 grant-related publication. Overall academic productivity increased after the award, and the majority of awardees report a positive or very positive impact of the award on their careers. Medical professional societies are an important sponsor of clinical research.

Minimizing Radiation Exposure During ERCP by Avoiding Live or Continuous Fluoroscopy.

GOALS: The aim of this study was to assess the cumulative radiation exposure incurred by patients when using single-frame fluoroscopy. BACKGROUND: Single-frame fluoroscopy is a technique that can be used instead of pulsed fluoroscopy or continuous live fluoroscopy to minimize radiation exposure during endoscopic retrograde cholangiopancreatography (ERCP). STUDY: We retrospectively reviewed ERCPs performed at our academic medical center. We recorded fluoroscopy time (FT, minutes), total radiation dose (mGy), dose area product (DAP, Gy cm²), and effective dose (ED, mSv). ERCP degree of difficulty was graded based on procedure complexity level. RESULTS: There were 400 ERCP procedures performed on 210 patients, 32 ERCPs were unsuccessful. The mean FT for all procedures was 1.57 minutes (median, 1.2 min); the mean FT for complexity score 1 procedures (0.78 min) was significantly shorter than for all other procedures (P<0.0001). The mean total radiation dose delivered for all procedures was 23.02 mGy (median, 14.95 mGy). The total radiation dose for complexity score 1 procedures (13.15 mGy) was significantly lower than for all other complexity scores (P<0.0001). The mean total DAP was 3.62 Gy cm² and the mean ED was 0.94 mSv. Procedure complexity score 1 DAP (2.1 Gy cm²) and ED (0.55 mSv) were significantly lower than for all other procedures (P<0.0001 for both). There was no statistically significant difference in these parameters when comparing successful and unsuccessful procedures. CONCLUSIONS: Successful ERCP can be performed using single-frame fluoroscopy only. Our results demonstrate lower radiation exposure using this technique than what is reported in the literature.

Large colorectal polyps: endoscopic management and rate of malignancy: does size matter?

BACKGROUND AND STUDY AIMS: High rate of malignancy has been reported in large colorectal polyps. However, studies were limited by including surgically resected polypoid lesions, only polyp ≥3 cm, only sessile polyps or carcinoma in situ. The aim of the study was to define the prevalence of invasive carcinoma among colorectal polyps ≥2 cm in diameter detected by colonoscopy and also to study the success of endoscopic resection. PATIENTS AND METHODS: All polypectomies of ≥2 cm colorectal polyps were identified from our endoscopy and pathology database and patients' medical records were reviewed for gross features, techniques of resection, complications, histology, and follow-up. Standard statistical tests were applied for calculating the rates, prevalence, and difference in proportions. RESULTS: Colonoscopic resection of 183 large polyps was performed in 174 patients over a period of 6 years (55% men and 45% women), mean age 64 years (median 67 y and range 25-91 y). The majority of polyps were sessile (84%). Fifty-six percent were located in the right colon. Invasive cancer was found in 10% of polyps. Endoscopic resection was successful in 89% of patients. Postpolypectomy bleeding and perforation was noted in 5% and 2% of patients, respectively. No death was observed. Seventy-eight percent of patients completed >1 year of follow-up after initial polypectomy. Recurrence of adenoma was noted in 12%, which was managed successfully by colonoscopic polypectomy techniques. CONCLUSIONS: The rate of invasive cancer is low among endoscopically resected large colorectal polyps and most of these polyps can be resected successfully via colonoscopy with minimal morbidity and no mortality. A close endoscopic follow-up is required to monitor for recurrence.

Correction to: Treatment of Rare and Aggressive Pancreatic Carcinosarcoma.

[This corrects the article on p. e00379 in vol. 7, PMID: 32607379.].

Treatment of Rare and Aggressive Pancreatic Carcinosarcoma.

A 42-year-old African American woman presented with 4 days of worsening midepigastric pain that radiated to her back. Computed tomography confirmed a diagnosis of acute pancreatitis and revealed a mass within the distal body and tail of the pancreas. After an endoscopic ultrasound with fine-needle aspiration yielding atypical cells suspicious for adenocarcinoma, the patient underwent an en bloc resection of the intra-abdominal mass with subtotal pancreatectomy, splenectomy, left colectomy, and left partial adrenalectomy. Histopathologic examination findings, in addition to immunohistochemical staining, revealed a diagnosis of pancreatic carcinosarcoma. Postoperatively, the patient has undergone 20 cycles of chemotherapy and has been transitioned to comfort measures at 16 months postoperatively because of progressive disease.

Acute acalculous cholecystitis simulating Mirizzi syndrome: a very rare condition.

Mirizzi syndrome, a rare complication of chronic cholelithiasis, is caused by an impacted stone in the cystic duct or the neck of the gallbladder. Patients present with abdominal pain, fever, and obstructive jaundice. The cholangiographic finding is a smooth stricture caused by lateral compression of the common hepatic duct. A similar appearance on cholangiogram can result from carcinoma of the gallbladder, carcinoma of the cystic duct, or hilar adenopathy. Acute acalculous cholecystitis simulating Mirizzi syndrome is extremely rare. This is the report of such a case in which marked inflammatory changes around the neck of the gallbladder likely caused significant mechanical obstruction of the common hepatic duct.

Malignant Granular Cell Tumor of the Bile Duct.

A 56-year-old man presented to the emergency department with painless jaundice and weight loss. Abdominal ultrasound detected dilation of the common bile duct and the intrahepatic bile ducts. Follow-up with endoscopic retrograde cholangiography exposed a stricture of the common hepatic duct, with cholangioscopy identifying an infiltrating tumor. Biopsy revealed a granular cell tumor, which was confirmed by positive S-100 immunohistochemical staining. Surgical excision confirmed granular cell tumor of the bile duct with morphological features suggestive of malignancy.

Endoscopic management of upper esophageal strictures after treatment of head and neck malignancy.

BACKGROUND: Dysphagia, usually due to proximal esophageal strictures, is a debilitating complication of therapy (surgery, radiotherapy, or chemotherapy) for head and neck malignancy. Scant attention has been given in the literature to the endoscopic management of these proximal esophageal strictures. OBJECTIVE: Our purpose was to assess the technical and functional outcomes of endoscopic management of proximal esophageal strictures after therapy for head and neck cancers. DESIGN: Retrospective case series. SETTING: Academic medical center. PATIENTS: Consecutive patients undergoing endoscopy and dilation of proximal esophageal strictures caused by chemoradiation or surgery for head and neck malignancy. MAIN OUTCOME MEASUREMENT: Technical and functional success after endoscopic dilation. RESULTS: Twenty-four patients were included. The mean age of patients was 70.4 years (range 42 to 82 years). The primary tumor site was larynx in 10 patients, oropharynx or hypopharynx in 4 patients, upper esophagus in 4 patients, and other sites in the remainder. Technical success (a luminal diameter of 42F or greater) was achieved in 80% of patients. Adequate dysphagia relief was achieved in 84% of patients whose esophageal stricture was dilated at least up to 42F. The average follow-up was 22 months (range 1-96 months). Repeat dilation was needed in 58% of patients. No complications or death occurred during the study period. LIMITATIONS: Retrospective design and highly selected patient population. Dysphagia assessment in conjuction with a speech pathologist was not performed in all patients. Results may not be applicable to other settings. CONCLUSION: In this case series, proximal esophageal strictures after treatment of head and neck malignancy were amenable to antegrade endoscopic dilation; however, no patient in our study had complete lumen obstruction. Repeat dilations are often needed and are effective in achieving and maintaining adequate dysphagia relief.

Lymphoepithelial cyst of pancreas. Role of endoscopic ultrasound guided fine needle aspiration.

Lymphoepithelial cysts of the pancreas are extremely rare, benign, nonneoplastic cysts that may simulate pseudocysts or cystic neoplasm of the pancreas. Endosonographic and cytologic features of pancreatic lymphoepithelial cysts are poorly characterized because of their rarity. However, appropriate prospective diagnosis of pancreatic lymphoepithelial cysts using endoscopic ultrasound-guided fined needle aspiration (EUS-FNA) cytology may permit conservative management because of their benign nature. We conducted a MEDLINE search using the MeSH terms "pancreas", "cyst" and identified 16 patients who were diagnosed with endosonography or computerized tomography (CT) guided fine needle aspiration. Usefulness and pitfalls of EUS- or CT-guided cyst fluid analysis in the pre-operative diagnosis of pancreatic lymphoepithelial cysts are discussed.

Single-step EUS-guided pancreatic pseudocyst drainage using a large channel linear array echoendoscope and cystotome: results in 11 patients.

CONTEXT: EUS-guided transmural drainage of pancreatic pseudocyst has been reported using a linear array echoendoscope; however, placement of large 10 French stent was not feasible because of the limited diameter of the working channel. Recently linear array echoendoscopes with large working channel (3.7 to 3.8 mm) and newer accessories for pancreatic cyst puncture have become available; however, clinical data on their efficacy and safety in pancreatic pseudocyst drainage is not available. OBJECTIVE: To evaluate efficacy and safety of a one-step real time EUS-guided pancreatic pseudocyst drainage approach using a 3.8 mm channel linear array echoendoscope and cystotome. DESIGN: Prospective case series. SETTING: Tertiary care hospital endoscopy unit. PATIENTS AND INTERVENTIONS: A total of 12 EUS-guided pancreatic pseudocyst drainage procedures were performed in 11 patients with symptomatic pancreatic pseudocyst using a 3.8 mm channel linear array echoendoscope and cystotome. MAIN OUTCOME MEASUREMENTS: Complete resolution of pancreatic pseudocyst on imaging. RESULTS: Successful puncture of pancreatic pseudocyst and placement of 1 or 2 stents (10 Fr) was successful in all patients who were considered eligible for EUS-guided pancreatic pseudocyst drainage. Overall 9 patients out of a total of 11 (82%) were managed successfully with EUS-guided pseudocyst drainage. Two recurrences were noted over a mean follow-up period of 4 months (range 3-6 months). One patient underwent successful repeat drainage and the other patient was managed with surgical cystogastrostomy because of infected cyst contents. No major complication occurred. LIMITATIONS: Uncontrolled, small sample size. CONCLUSIONS: A single-step approach using a large channel (3.8 mm) linear array echoendoscope and cystotome appears feasible. This approach appears safe and effective in managing selected patients with symptomatic pancreatic pseudocysts.

Gender-related differences in dyspepsia: a qualitative systematic review.

BACKGROUND: Relative to men, women are diagnosed more frequently with functional gastrointestinal (GI) disorders. With increased awareness of basic gender differences in perception and treatment of visceral pain, there has been new interest in research on gender disparity in the care of people with functional GI disorders. Past attention has focused on irritable bowel syndrome, whereas gender differences in other disorders are less well described. OBJECTIVE: Our aim was to systematically review studies that have examined gender-related differences among patients with dyspepsia. METHODS: MEDLINE, HealthSTAR, and PsycINFO databases were searched for English-language articles on dyspepsia published between 1966 and August 2001. Epidemiologic studies, clinical trials, review articles, and conceptual articles from peer-reviewed journals were included for review. Findings were summarized and discussed within a framework of biological and psychosocial factors. Statistical analysis of combined data was inappropriate because of the inconsistent definition of dyspepsia among different studies and wide variation in the types of articles reviewed. RESULTS: Studies that examine gender-related differences in patients with dyspepsia have focused their investigations on the clinical epidemiology and pathophysiology of dyspepsia. In most epidemiologic studies, no gender analysis was performed beyond a description of sample demographics, and when statistical significance was tested, few consistent gender differences were found. Overall, it appears that men and women with dyspepsia possibly differ with respect to pattern of symptoms, pain perception or modulation, and antinociceptive mechanisms, but these observations have not been confirmed. No study evaluated the clinical implications of these possible differences. CONCLUSIONS: Future efforts should be directed to not only examine gender-related differences in the clinical epidemiology of dyspepsia, but also understand their clinical significance. Therefore, well-designed population-based studies using a consistent definition of dyspepsia are needed to investigate the prevalence of dyspepsia symptoms and patterns of dyspepsia management among men and women.

Urbanization and coronary heart disease: a study of urban-rural differences in northern India.

BACKGROUND: In the West, urbanization has been accompanied by a rise in the rate of coronary heart disease. This trend has gone hand in hand with an increased consumption of processed, energy-dense food and dependence on machines for physical work. To examine whether a similar trend is underway in northern India, the prevalence of and risk factors for coronary heart disease were compared in rural, semi-urban and urban communities. METHODS AND RESULTS: A total of 7,169 adults were interviewed and examined during 1995-2000 in cross-sectional cluster sample surveys from a rural area of Haryana (Raipur Rani block), two semi-urban areas of Punjab (Mandi Gobindgarh and Morinda), and Chandigarh city. The study, which covered people in the age-group of 35+ years, also estimated the lipid, glucose and insulin levels of a sub-sample of 186 persons who did not have coronary heart disease or hypertension. The prevalence of coronary heart disease among males in the villages, towns and city was 1.7%, 2.5% and 7.4%, respectively, and among females, 1.5%, 3.4% and 7.1%,respectively. The age- and sex-adjusted prevalence odds ratio of coronary heart disease, in comparison to the villages, was 1.9 (95% CI; 1.1-3.2) in the towns and 4.9 (95% CI: 2.9-8.2) in the city. Hypertension, diabetes, obesity and physical inactivity were significantly more common in the urban areas, while the rate of tobacco smoking was significantly higher in the rural areas ( p< 0.05). The alcohol consumption rates for the urban and rural communities were similar (p> 0.05). The quantity of the food items commonly consumed, as well as the frequency with which particular items were consumed, varied across the rural, semi-urban and urban areas ( p< 0.05). The urban population had significantly higher levels of lipids and serum insulin than did the rural population, but a lower level of plasma glucose ( p< 0.05). CONCLUSION: The urban way of living is leading to an increase in the prevalence of the well-known risk factors for, as well as the rate of, coronary heart disease. Attempts to preserve the traditional lifestyle are necessary in order to prevent an epidemic of coronary heart disease in the developing countries.

Pancreatic tuberculosis diagnosed with endoscopic ultrasound guided fine needle aspiration.

CONTEXT: Isolated pancreatic tuberculosis is rare in the Western world. Its clinical presentation often mimics pancreatic malignancy and the diagnosis is usually not suspected or confirmed prior to laparotomy. Endoscopic ultrasound guided fine needle aspiration cytology has proved to be an excellent tool for the cytological diagnosis of pancreatic and peripancreatic masses. However, this technique has not been reported for diagnosing pancreatic or peripancreatic tuberculosis. CASE REPORT: We describe a 57-year-old South Asian man with pancreatic tuberculosis who presented with fever of undetermined origin and a pancreatic mass on imaging. He was successfully treated with anti-tuberculosis regimen following confirmation of his diagnosis with endoscopic ultrasound guided fine needle aspiration cytology. CONCLUSIONS: Pancreatic tuberculosis should be suspected in patients having a pancreatic mass, particularly if patient presents with fever and lived in, or traveled to, an area of endemic tuberculosis or exposed to tuberculosis. When the diagnosis is suspected, endoscopic ultrasound guided fine needle aspiration cytology of the pancreatic lesion can confirm the diagnosis and so avoid an unnecessary explorative laparotomy or pancreatic resection.